Structural characterization and pharmaceutical properties of three novel cocrystals of ethenzamide with aliphatic dicarboxylic acids.

Ethenzamide (ET) was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover materials of improved physicochemical properties, that is, higher solubility and better stability. Three novel cocrystals of ethenzamide with glutaric, malonic and maleic acids were obtained by neat grinding and slow evaporation from solution. The purpose of the study was to notice the changes in the geometry and interactions of ET molecule in crystalline phase introduced by different acid and relate them to physicochemical properties of pure ethenzamide. Therefore, the crystal structure of the cocrystals was determined by single-crystal X-ray diffraction analysis. The powder samples were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, 13 C and 15 N solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of chemical shielding constants. The high stability of cocrystals during direct compression was proved. The solubility in simulated gastric fluids for studied cocrystals appeared to be approximately 1.6 times-fold higher than ethenzamide. The dissolution rates of all ethenzamide cocrystals were not faster than the pure drug, but after 240 minutes more drug was released.